I Dr.E.Muralinath providing information regarding humoral and nervous regulation of BP and Fetal circulation.

1. Circulation
Dr. E. Muralinath
Associate Professor,
College of Veterinary Science, Proddatur, Andhra
Pradesh

2. Microcirculation
 Circulation in the tissues
 Includes arterioles, capillaries, venules & lymph channels
 Exchange of gases & nutrients
 Small arterioles and metarterioles control blood flow to
each tissue
 Small arterioles are controlled by tissue needs
 Each tissue controls its own blood flow - autoregulation
 10 billion capillaries with a total surface area estimated at
500 - 700 m2

3. Structure of Microcirculation
 Arterioles: small arteries branches 6 - 8
times to form arterioles (D = 10 -15 μm),
muscular, capable of vasomotion
 branch 2-5 times - metarterioles (5-10
μm)
 metarterioles & precapillary sphincters
vary near to tissues served
 directly affected by tissue conditions
(e.g., nutrient & metabolic end product
conc.
 Venules: Significantly larger than
arterioles, have weaker muscular walls
 pressure in venules < arterioles
 Veins contract despite weak walls
 functional cells are within 20 to 30 μm
from the nearest capillary

4. Capillaries are 0.5 -1 μm thick, and
5-9 μm long
Capillary Pores: intercellular clefts
6-7 nm, 20X > H20 molecules) and
plasmalemmal vesicles
Brain: tight junctions allow only
gases & water
Liver: clefts are wide open, allow
plasma proteins to move in & out
GIT: midway to Liver & muscles
Kidneys: fenestrae allows large
amounts of molecules &
electrolytes to pass through
Structure of Microcirculation

5. Blood flows intermittently in capillaries due to smooth muscle
activity in metarterioles & precapillary sphincter, ‘vasomotion’
Cause of vasomotion: Oxygen utilization in tissues
↑ oxygen utilization by the tissue, ↓ conc. of oxygen in
capillaries,↑ the frequency & duration of intermittent blood flow
Average function of capillary system: an average rate of blood
flow, an average capillary pressure, an average rate of transfer of
substances between the capillary bed & interstitial fluid
Mode of transfer − Diffusion, Filtration (Slit pores) & Pinocytoses
(Vesicles) – Diffusion is quantitatively more important
hydrophilic substances: H2O,Na+ Cl− glucose & urea (D)
 lipophilic substances: trans-endothelial movement, CO2 & O2
Microcirculation − Vasomotion

6. Microcirculation – Capillary Permeability
 Net rate of diffusion (NRD): NRD ∞ to the concentration
difference between the two sides of the membrane
 NRD ∞ Concentration gradient x permeability
 Slight concentration gradient causes a net diffusion of large
quantities

7. Frank - Starling Forces
Interstitial fluid: 1/6th of total volume of the body is intercellular
spaces filled with fluid
Hydrostatic & Colloid Osmotic Forces (four) determine NRD, referred
to as ‘Starling forces‘ or Filtration pressure
Capillary pressure (Pc): force fluid out of capillary wall into the
interstitial spaces
Interstitial fluid pressure (Pif): force fluid into the capillary when Pif
is positive, and outside when Pif is negative
Capillary plasma colloid osmotic pressure (Pp): cause osmosis of
fluid inward through the capillary membrane from interstitial
spaces
Interstitial fluid colloid osmotic pressure (Pif): cause osmosis of
fluid outward through the capillary membrane into interstitial
spaces

8. Frank − Starling Forces

9.  Negative ISF pressure is due to pumping of fluid out by the
Lymphatics
 COP of plasma and ISF is due to Proteins, Albumin,
Globulin and others
 Considerable amounts of proteins leak into ISF from
capillaries
 Absolute quantity of proteins in ISF > plasma
 Volume of ISF is 4 times more than plasma volume
 Concentration of proteins in ISF < plasma
 COP of plasma, ISF and negative ISF pressure is same at
the venous end & arterial end
Frank - Starling Forces

10.  The sum of all these forces is called net filtration pressure
NFP = Pc − Pif + πif − πp
If net filtration pressure is positive: fluid forced outward
If net filtration pressure is negative: fluid forced inward
NFP is slightly positive in normal conditions, resulting in a net
filtration of fluid out into the interstitial space in most organs
Starling Forces – ∆P at Arterial End
NFP = Pc − Pif + πif − πp
NFP = 30 −(− 3)+ 8 -28 = 13

11. Starling Forces – ∆P at Venous End
NFP = Pc − Pif + πif − πp
NFP = 10 −(− 3)+21 −28 = 7

12. Starling Forces –Average ∆P in Capillaries
NFP = Pc − Pif + πif − πp
NFP = 17.3 −(− 3)+ 8 -28

13.  Amount filtered out = Amount reabsorbed
 Net filtration pressure outward is 28.3 – 28.0 = 0.3 mm Hg
 Net filtration rate throughout body = 2ml/min
 Average net filtration pressure = 0.3 mm Hg
 Whole body capillary filtration coefficient?
=
𝟐 𝐦𝐥
𝐦𝐧 𝐗 𝟎.𝟑 𝐦𝐦. 𝐨𝐟 𝐇𝐠
= 6.67ml. min-1. mm. Hg-1
 If filtration forces ↑, oedema occurs
 If reabsorption forces ↑, dehydration occurs
 Filtration coefficient /100g of tissue = 0.01 ml. min-1. mm Hg-1
Whole body capillary filtration coefficient

14. Lymphatic System
 Lymphatic vessels are thin walled
 Lymph is formed from interstitial fluid (ISF)
 Lymphatics remove excess fluid from interstitium
 In superficial skin, CNS, muscle endomysium and
bones, prelymphatics connect to Lymphatics
 Lymphatics empty into right and left subclavian veins at
their junction with internal jugular veins
 Protein conc. of lymph is different in different tissues

15.  Anchoring elements attach endothelial
cells to surrounding tissues
 Endothelial cells edges overlap to form
valves
 Valves opens only into the lymphatic
capillary
 Smooth muscles walls of lymph
capillaries help in moving lymph
 ISF push these valves open & allow flow
directly into lymph vessels
Lymphatic Capillaries
1/10 of the fluid that passes through
capillaries returns to circulation via. the
lymphatics ( 2 to 3 litres/day)

16. Contraction of Lymphatics
 Intrinsic contraction
Fluid accrual stretches walls causing
reflex contraction of smooth muscles
Intra vessel pressure increases and
valves open (up to 50mm Hg)
Successive segments operate
independently
 Extrinsic contraction
Contraction of muscles, movement of
body parts, arterial pulsations,
compression of tissue by objects outside
body, all increase lymph flow
Exercise increases lymph flow by 10-30X,
While rest reduces lymph flow

17. Lymph flow changes with ISF pressure
changes
If negative ISF pressure > 0, lymph
flow increases to 20X
Factors that increase ISF volume,
pressure and lymph flow
↑capillary pressure
↑plasma COP
↑ conc. Of protein in ISF
↑permeability of capillaries
↑ in ISF pressure >2-3 mm Hg
Rate of lymph flow
lymph flow↓ if lymph vessels collapse
lymph flow ∞ degree of lymph pump activity

18. Hydraulic Conductivity of Lymphatics

19. Higher ISF & Edema

20. Lymphatics function
 Fluids are moved from ISF into blood circulation
 Brings in proteins from ISF to circulation
Blood capillaries cannot reabsorb proteins
If proteins are not removed from ISF on regular basis, an
animal would die within 24h
 Regulate ISF volume, conc. & pressure
 Remove bacteria from tissues & lymph glands eliminate them
 Major route of absorption in GIT
 the rate of lymph flow ∞ Interstitial fluid pressure X Activity
of the lymphatic pump

21. Basic Theories Of Circulation

22. Blood Flow Control
 Importance of circulation
 delivery of oxygen & nutrients to the tissues
 removal of CO2 & H2
 maintain optimal concentrations of ions
 transport of hormones & other factors
 other needs - thermoregulation, glomerular filtration
 Tissues control local blood flow according to their own
metabolic & oxygen demands
 Intrinsic, independent of neural & hormonal effects
 WHY is it important to have a controlled blood flow to
tissues?
 takes lot more blood than the heart can pump
 maintain minimal supply required to meet the tissue needs

23. Blood Flow Control

24. Blood Flow Control
 Two phases of local flow control: Acute vs. Long term
 Rapid vs. slow
 Seconds/minutes vs. days, weeks or months
 vasodilatation/constriction of vessels vs. altered physical
size/number of supplying blood vessels
 Acute control rapidly restores normal flow to local tissues
Metabolism Oxygen sat.

25. Acute control of local blood flow in response to changes in
tissue metabolism and oxygen supply modulates contractility
of resistance vessels---------vasoconstriction or vasodilation
(arterioles, metarterioles, pre-capillary sphincters)
 Two theories of local blood flow in response to changing
metabolic needs of the tissue
 Vasodilator theory
 Oxygen-lack theory/nutrient lack theory

26. Vasodilator Theory
release of vasodilator substances
High metabolic rate (exercise), lower blood flow
(higher BP), short O2 supply (high altitudes),
nutrients shortage (starvation) and decreased
quantities of available oxygen (hypoxia)
act on smooth musculature of arterioles,
metarterioles and pre-capillary sphincters
increases blood flow and oxygen supply
cause relaxation/dilatation of blood vessels

27. Oxygen/Nutrient Lack Theory
deficient supply causes vasodilatation
decreased oxygen, glucose, amino acids,
vitamins (B-complex) required for optimal
smooth muscle contraction in blood vessels
opens pre-capillary sphincters of large
number of capillaries
high tissue levels/ precapillary sphincters
closed till nutrients utilized
activating more tissue units
low tissue levels/Precapillary sphincters
kept opened until restored

28. Both vasodilator & oxygen lack theory work together, in
varying ratios, in different conditions
Active hyperemia
higher blood flow in a highly active tissue
more vasodilator substances released
E.g., thinking brain, exercising muscle or secreting
GIT glands
 flow may increase to as high as 20X normal
Reactive hyperemia
 increased blood flow after infarction, embolism etc.
 flow may continue from sec to hours, until tissue
oxygen debt repaid
 mainly an effect of metabolic blood flow regulation
Metabolic Control

29.  Myogenic theory
 contractile properties of smooth muscle fibers stretching due
to suddenly ↑Blood Pressure(BP) - ↑cytosolic calcium in
smooth muscles → vasoconstriction & ↓blood flow
 relaxation due to ↓BP - ↓cytosol calcium levels in smooth
muscles → vasodilation & ↑ blood flow
 Metabolic theory
 autoregulation is by metabolic end products
 blood carries metabolic end products away from tissues
 ↓flow → ↑end products in tissue → vasodilation → ↑flow
 ↑flow → ↓end products → vasoconstriction → ↓flow
Autoregulation - arterial pressure changes
 Acute changes in BP alter local blood flow to tissues
 “autoregulation” is explained by two theories

30. Special Cases of Acute Flow Control
 Kidneys
 tubuloglomerular feedback mechanism
mediated by macula densa
filtered excess fluid in distal tubules sensed by macula densa
leads to afferent arteriole constriction, decreased blood flow
and decreased glomerular fluid filtration
 Brain
concentrations of CO2 and hydrogen ions in brain tissue
increased concentrations causes cerebral blood vessel
dilatation
washout of excess CO2 and hydrogen ions restores normalcy
Skin
blood flow increases to skin capillaries in hot environments
to dissipate excess heat

31. Dilatation of Upstream blood vessels
local mechanisms can only dilate small arterioles and
capillaries, not arteries
vasodilators cannot reach beyond vessels of a tissue unit
increased blood flow through microcirculation is possible
only by dilatation of upstream arteries in response to local
tissue needs
in response to shear stress induced by rapid blood flow,
endothelium of small vessels secrets endothelial derived
relaxing factor (EDRF)
principal component of EDRF is Nitric oxide (NO, gas) which
is a short lived vasodilator (half life of 6 sec)
NO causes vasodilatation of upstream arteries and facilitates
increased local tissue blood flow

32. Flow, Pressure and Resistance

33. Flow, Pressure and Resistance
 Blood flows from high pressure to low, pressure areas
 Pressure difference (P1−P2), Units of resistance, R = dynes x s/cm5
𝑭𝒍𝒐𝒘 (𝒎𝑳/𝒔𝒆𝒄) =
𝑷𝒆𝒓𝒇𝒖𝒔𝒊𝒐𝒏 𝒑𝒓𝒆𝒔𝒔𝒖𝒓𝒆 (∆𝑷)
𝑹𝒆𝒔𝒊𝒔𝒕𝒂𝒏𝒄𝒆
 E.g., Perfusion pressure = 90 mm. Hg; Vent. output= 90 mL/s
𝐹𝑙𝑜𝑤 (𝑅) =
90 𝑚𝑚.𝐻𝑔
90 𝑚𝐿/𝑠𝑒𝑐
= 1 R unit
 Blood flow measured by Doppler flow meter, plethysmograph

34. Factors Determining Blood Flow
 Pressure gradient ∝ flow
 Resistance ∝
𝟏
𝐟𝐥𝐨𝐰
(mainly by arterioles)
 Viscosity ∝
𝟏
𝐟𝐥𝐨𝐰
(RBC count, plasma proteins)
 Diameter ∝ flow (Aorta – elasticity/recoiling effect, arterioles –
sympathetic tone, CSA)
 Velocity ∝ flow (Cardiac output, CSA, Viscosity)

35. Blood flow
 Blood flow: laminar (streamline) vs. turbulent (noisy)
 Probability of turbulence, Re= Reynolds number: the critical
velocity at which flow becomes turbulent
𝑹𝒆 =
𝝆𝑫𝑽 (inertial factor)
𝜼 (𝒗𝒊𝒔𝒄𝒐𝒖𝒔 𝒇𝒂𝒄𝒕𝒐𝒓)
 Re =Reynolds number, ρ (Rho) = fluid density, D = diameter , V
= flow velocity and η (eta) = fluid viscosity
 Re < 2000 – linear flow; Re > 3000 – turbulent flow

36. Blood flow & velocity
 Flow vs. Velocity: volume per unit time (cm3/s) vs. linear
displacement per unit time (eg, cm/s)
 Mean blood flow (𝐐) = volume of blood that flows into a region of
circulatory system in a given unit of time
 Flow, 𝐐 𝐦𝐋. 𝐦𝐢𝐧
− 𝟏 = 𝐕 (𝐦𝐦. 𝐬
− 𝟏) x A (𝐂𝐒 𝐚𝐫𝐞𝐚, 𝐜𝐦𝟐)
 Mean blood velocity (V): Distance travelled by a volume of blood in
a unit time through a specific blood vessel
𝐕(𝐦𝐦. 𝐬
− 𝟏) =
𝐐 (𝐦𝐋. 𝐦𝐢𝐧
− 𝟏)
𝐀 (𝐂𝐫𝐨𝐬𝐬 𝐬𝐞𝐜𝐭𝐢𝐨𝐧𝐚𝐥 𝐚𝐫𝐞𝐚, 𝐜𝐦𝟐)
 Mean velocity aorta> smaller vessels>capillaries
 The peak velocity occurs during maximal ventricular ejection

37. Viscosity
 Plasma is 1.8 times more viscous than
water
 whole blood is 3–4 times more viscous
than water, e.g., immunoglobilinemia,
hereditary spherocytosis
 In large vessels, ↑ haematocrit ↑
viscosity
 In arterioles, capillaries, and venules
viscosity change /unit haematocrit
change is smaller vs. large vessels
 In polycythaemia (haematocrit is 60 or
70), the blood viscosity can be 10 times
more vs. water, and flow through blood
vessels is greatly retarded

38. Hagen-Poiseuille equation: Flow (Q) is directly proportional to
pressure gradient (PA – PB), fourth power of radius (r4), but inversely
proportional to the length of the tube (L) & viscosity (η) . Therefore,
flow rate F = (PA – PB) × ( π/8 ) × ( 1/η ) × ( r4 /L)
𝑭 =
𝑷𝟏−𝑷𝟐 π𝒓𝟒
𝟖 (𝑳 𝑿 η)
 Arterioles change their radius between 8-30μm, so blood flow could
change ~256 times
 Windkessel (elastic reservoir) effect: recoiling effect of blood
vessels that converts the pulsatile flow into continuous flow
 Mean velocity in aorta is ≥ 50 cm/second
 systole: up to 120 cm/s vs. diastole: zero or negative (Pulsatile)
 flow through other blood vessels is continuous
 Windkessel vessels maintains continuous flow of blood through
the circulatory tree by acting as a second pump

39. Conductance
It is the blood flow through a vessel at a given pressure
gradient, ml/S/mm Hg
Conductance =
𝟏
𝑹𝒆𝒔𝒊𝒔𝒕𝒂𝒏𝒄𝒆
When the blood flow is laminar, small diameter changes
causes tremendous changes in conductance
Conductance ∞ (diameter)4

40. Shear Stress
 Force applied by the flowing blood on the endothelium in the
direction of flow/parallel to the long axis of the blood vessel
 Due to viscous drag of blood against vascular walls
𝜸 = 𝜼
𝒅𝒚
𝒅𝒓
Shear stress (γ), viscosity (η, eta) and rate (dy/dr)
 This stress releases NO from endothelial cells
 NO relaxes blood vessels, ↑diameter of the upstream arterial
blood vessels in response to ↑micro-vascular blood flow
downstream
 Effectiveness of local blood flow control is enhanced

41. Vascular distensibility & Compliance
 Vascular distensibility: fractional increase in blood volume
in a blood vessel for each mm. of Hg. pressure rise
 𝐃𝐢𝐬𝐭𝐞𝐧𝐬𝐢𝐛𝐢𝐥𝐢𝐭𝐲 =
𝐈𝐧𝐜𝐫𝐞𝐚𝐬𝐞 𝐢𝐧 𝐛𝐥𝐨𝐨𝐝 𝐯𝐨𝐥𝐮𝐦𝐞
𝐈𝐧𝐜𝐫𝐞𝐚𝐬𝐞 𝐢𝐧 𝐩𝐫𝐞𝐬𝐬𝐮𝐫𝐞 𝐗 𝐎𝐫𝐢𝐠𝐢𝐧𝐚𝐥 𝐯𝐨𝐥𝐮𝐦𝐞
 arteries are 8X less distensible than veins & pulmonary
arteries are 6X more distensible than systemic arteries
 Vascular compliance/ Capacitance: total volume of blood
that can be stored in a given portion of the circulation for each
mm. of Hg. (pressure) rise
 C𝐨𝐦𝐩𝐥𝐢𝐚𝐧𝐜𝐞 =
𝐈𝐧𝐜𝐫𝐞𝐚𝐬𝐞 𝐢𝐧 𝐛𝐥𝐨𝐨𝐝 𝐯𝐨𝐥𝐮𝐦𝐞
𝐈𝐧𝐜𝐫𝐞𝐚𝐬𝐞 𝐢𝐧 𝐏𝐫𝐞𝐬𝐬𝐮𝐫𝐞
 Veins are called capacitance vessels

42.  Compliance = distensibility x original volume
 a highly distensible vessel that has a slight original volume
may have less compliance compared to a much less
distensible vessel that has a large original volume
 E.g., a highly distensible bld. Vessel with a original
volume of 100 mL, new volume is 120 mL, distensibility
=
20
1
x 100 = 0.2 and compliance = 0.2 x 20 = 4
 E.g., a less distensible bld. Vessel with a original volume
of 1000 mL, new volume is 1020 mL, then the
distensibility =
20
(1 𝑥 1000)
= 0.002, compliance = 0.002 x
200 = 0.4
Vascular distensibility & Compliance

43. Flow & Cross-Sectional Area
As same volume of blood must flow through each segment of the
circulation every minute, the velocity of blood flow is inversely
proportional to vascular cross-sectional area.

44. The cross-sectional area of aorta is 0.8 cm2, large arteries is 3.0
cm2 and capillaries is 600 cm2
Parts
Velocity of blood flow
(cm/sec)
Aorta 13
Large arteries 6
Arterioles 0.3
Capillaries 0.05
Venules 0.1
Veins 1.0
Vena cava 9
Velocity of Blood Flow in Dogs

45. Total Peripheral Vascular Resistance
The resistance to blood flow of the entire systemic
circulation is called the total peripheral resistance
Measured in peripheral resistance units (PRU)
If P = 1mm Hg and F = 1ml/s, then R = 1 PRU
Ex: In an average adult, F = 100ml/s (Cardiac output) and P
= 100 mm Hg (between systemic arteries and systemic
veins), then the resistance is 1 PRU
Powerful vasoconstriction: Resistance to ↑4X (4 PRU)
Extreme Vasodilatation: Resistance to ↓5X (0.2PRU)

46. Total Pulmonary Vascular Resistance
 The resistance to blood flow in the pulmonary circulation is
called the total pulmonary vascular resistance
 Mean pulmonary arterial pressure = 16 mm Hg
 Mean left atrial pressure = 2 mm Hg
 Net pressure difference = 14 mm Hg
 cardiac output = 100 ml/sec
 the total pulmonary vascular resistance = 14/100= 0.14 PRU,
about one seventh that in the systemic circulation)

47. Circulation Time
 Time taken by blood to travel through one part or entire
circulatory system
 Pulmonary circulation time: transit time from a major
vein to lungs. E.g., injecting a substance (histamine)
and measure the time taken to see flushing of face
 circulation time from arm vein to face: 24 seconds
 Number of heartbeat/total circulation time, is same for most
mammalian species, ≈ 30 beats/total circulation time
 Circulation time ↓, if velocity of blood flow ↑ & vice versa
 Prolonged circulation time: Polycythaemia, heart failure
 Decreased circulation time: Exercise, adrenaline rush, anemia

48. Blood Pressure

49. Blood pressure
Lateral pressure exerted by a circulating column of blood against any
unit area of the arterial wall (Stephen Hales (1730) )
Expressed in four different parameters
Systolic blood pressure
Diastolic blood pressure
Pulse pressure
Mean arterial blood pressure
Systolic pressure: maximum pressure exerted during cardiac systole
(increased blood volume & distension of arterial walls)
Diastolic pressure: minimum pressure exerted during cardiac diastole
(less distension & lower blood volume in arteries)
Pulse pressure: systolic pressure − diastolic pressure (120 − 80 = 40
mm. Hg.)
Mean arterial pressure: average pressure that exists in arteries
throughout one cardiac cycle, systole, and diastole.

50. Blood Pressure
Systolic pressure: indicates the total kinetic energy
imparted to the blood by the heart.
Diastolic pressure: reflects the state of peripheral vessels
and load on vascular wall
Pulse pressure: ventricular output and measure the
variations of kinetic energy of heart. Values increases and
decreases with increase and decrease of stroke volume
Mean arterial pressure (MAP): useful to find out pressure
in major arteries distal to aorta but not in aorta because
the pattern of arterial pressure pulsation change as the
pulse moves away from the heart

51. Mean Arterial Pressure (MAP)
MAP = 60% of Diastolic Pressure + 40% of Systolic Pressure
Arterial pressure = Cardiac output x Total Peripheral Resistance
 MAP is measured millisecond by milliseconds over a time period
 As the arterial pressure is closure to diastolic pressure than to
systolic pressure during greater part of the cardiac cycle (also
diastole period is longer than systole period (almost twice), MAP is
closer to diastolic pressure value
Mean arterial blood pressure = Diastolic 𝒑𝒓𝒆𝒔𝒔𝒖𝒓𝒆 +
𝑷𝒖𝒍𝒔𝒆 𝒑𝒓𝒆𝒔𝒔𝒖𝒓𝒆
𝟑
= 80 +
𝟒𝟎
𝟑
= 93.3 mm Hg

52. Standard Units of Pressure
Arterial Blood Pressure: Expressed in millimeters of mercury (mm
Hg), as the mercury manometer has been used since its invention
Millimeters of Mercury (mm. of Hg.): if pressure in a vessel is 50 mm
Hg, means that the force exerted is sufficient to push a column of
mercury against gravity up to a level of 50 mm high, and at 100 mm
Hg, it will push the column of mercury up to height of 100 mm
Centimeters of Water (cm H2O): a pressure of 10 cm H2O means a
pressure sufficient to raise a column of water against gravity to a
height of 10 centimeters
One mm Hg Pressure = 1.36 cm H2O pressure, because the specific
gravity of mercury is 13.6 times of water’s, and 1 cm =10 mm
One millimetre of Mercury = 0.133 kPa (kilo pascal), so in SI units this
value is 16.0/9.3 kPa

53. Pulse Pressure Drives Blood Flow
BP is highest in aorta (98 mm Hg), moderate in capillaries
and lowest in the vena cava (3 mm Hg)
Maximal pressure gradient is 95 mm. Hg. (98 – 3 mm.
Hg.) that drives blood flow to aorta to vena cava
RV
LV
RV
LV

54. Heart pumps blood into aorta in a pulsatile manner
Arterial pressure alternates between a systolic pressure (120 mm
Hg) and a diastolic pressure level (80 mm Hg), averaging about
100 mm Hg
As the blood flows through the systemic circulation - mean
pressure falls progressively – at the termination of the vena cava
(0 mm Hg)
The pressure in the systemic capillaries
arteriolar ends: 35 mm Hg
venous ends: 10 mm Hg
average “functional” pressure in vascular beds: 17 mm Hg, (a
pressure low enough that little of the plasma leaks through the
minute pores of the capillary walls)
nutrients can diffuse easily to the outlying tissue cells
Systemic Circulation
LV
RV

55. In the pulmonary arteries, the pressure is also pulsatile - but the
pressure level is far less than that in systemic arteries
Pulmonary artery systolic pressure: 25 mm Hg
Pulmonary artery diastolic pressure: 8 mm Hg
Average: 16 mm Hg
The mean pulmonary capillary pressure is around 7 mm of Hg
Each minute, Flow, 𝐐 𝐭𝐡𝐫𝐨𝐮𝐠𝐡
 lungs = systemic circulation = heart = Cardiac output
The low pressures of the pulmonary system – ensures adequate
time of exposure of the blood in the pulmonary capillaries to
oxygen and other gases while traversing alveolar walls
Pulmonary Circulation
LV
RV

56. Parts
Velocity of
blood flow
(cm/sec)
Aorta 13
Large arteries 6
Arterioles 0.3
Capillaries 0.05
Venules 0.1
Veins 1.0
Vena cava 9
Blood Pressure, Flow & Velocity
Systole Diastole Systole

57.  Pressure − volume (P-V) relation
in arterial system blood
 700 mL– AP 100 mm. Hg
 400 mL of blood – AP 0
mm. Hg
 Veins have high capacitance
 even with 2−3 L blood,
changes in pressure are trivial
(3 − 5 mm. Hg, < 20 mm Hg)
 Sympathetics alter P-V relations
 increases cardiac function
 circulation works normally
even when 25% of total blood
is lost, e.g., traumas
Pressure Volume − Arteries & Veins

58. Delayed Compliance
 ↑blood volume at first ↑pressure, but delayed compliance ↓
pressure back to normal within a minute to an hour – delayed
compliance
 due to immediate elastic distention, stress relaxation
 opposite in case of blood loss
 converts pulsatile blood flow into continuous
 Pulse pressure: SP − DP = e.g., 120 – 80 = 40 mm. of Hg
 stroke volume & compliance (distensibility)

59.  Arteriosclerosis
 ↑ Pulse pressure
 Aortic stenosis
 ↓Pulse pressure
 Patent ductus arteriosus
 Aorta – Pulmonary artery shunt
 ↓ Diastolic pressure
 Aortic regurgitation
 Incompetent or absence of
aortic valve
 ↓Pulse pressure
Pulse Pressure
 Pulse pressure ↑ & ↓ with ↑ & ↓ of stroke volume (SV)
 When SV constant, Pulse pressure =
𝒔𝒕𝒓𝒐𝒌𝒆 𝒗𝒐𝒍𝒖𝒎𝒆
𝒄𝒐𝒎𝒑𝒍𝒊𝒂𝒏𝒄𝒆 𝒐𝒇 𝒂𝒓𝒕𝒆𝒓𝒊𝒂𝒍 𝒕𝒓𝒆𝒆

60. Pressure Pulse Transmission & Damping
Blood vessels Transmission rate
Aorta 3 - 5 m/sec
Large arteries 7 - 10 m/sec
small arteries 15 - 35 m/sec
 Greater compliance → lesser velocity,
low rate of pulse pressure transmission
 In aorta, pressure pulse transmission
velocity is 15-20 times > flow velocity
 Intensity of pulsation is lowest in the
capillaries (damping) because of high
resistance and less compliance
 Damping α
𝟏
compliance x resistance

61. Auscultatory method: BP is measured using stethoscope
Palpatory method: pulse is used to find systolic
pressure only
Ultrasound Method: In this method, the Korotkoff’s
sounds are amplified using piezoelectric microphones
mounted within or below the cuff. The electric signal
obtained is amplified to increase the audibility
Microphone Method: In this method ultrasound is used
to detect arterial wall movement as pressure is
decreased with the blood pressure cuff
Methods of BP Measurement

62. Direct Method
Animal should be anesthetized
Carotid artery can be connected to
any of: the mercury manometer,
membrane manometer, optical
manometer, to record BP
Mercury manometer is a `U' glass
tube containing mercury in one limb
and 10% sodium citrate in the
opposite limb to balance the
mercury. The limb with sodium
citrate is connected to carotid artery
through a tube with a cannula at its
end. The float over the mercury
column will record the BP over the
kymograph

63. Measurement of BP - Indirect Method
 Clinically auscultation, pressure pulsation in major arteries heard with a
stethoscope. E.g., human(brachial artery), dog (femoral artery), cattle
(middle coccygeal artery)
 Measured when external pressure > systolic pressure, is applied to a major
artery until blood flow through that artery is stopped and no sounds are
heard (KOROTOKOFF sounds)
 When the external pressure is slowly released blood flow resumes and
sounds begin to be heard –
 Phase I: Clear tapping sound for two successive beats, systolic pressure
 Phase II: Softening of tapping sound & addition of swishing sound
 Phase III: Return of tapping sounds with more intensity & sharpness
 Phase IV: Abrupt of muffling of sounds, exhibiting a soft blowing quality
 Phase V: Complete disappearance of all sounds, diastolic pressure
 These sounds are called KOROTOKOFF sounds (Nikolai Korotkoff
Auscultatory method)

64. Representative Adult Blood Pressures

65. Mean Circulatory Filling Pressure
The pressure in the entire (systemic & pulmonary)
static circulatory system (no blood motion), and no
pressure difference between the aorta and the vena
cava, is called mean circulatory filling pressure (7 mm
Hg)
Circulatory filling pressure is caused by the static
blood distending the blood vessels; the vessels being
elastic, they recoil and this recoiling accounts for the
pressure in the static circulation

66. Basic Theory of Circulatory Function
The rate of blood flow to each tissue of the body is almost
always precisely controlled in relation to the tissue needs
Active tissue demands more nutrients
Heart can increase its cardiac output 4 −7 times over resting
levels
The micro-vessels of each tissue continuously monitor tissue
needs - dilation or constriction - to control local blood flow
Nervous control of the circulation from the central nervous
system provides additional help in controlling tissue blood flow

67. Cardiac output regulated by sum of all the local tissue flows
Arterial pressure is independent of either local blood flow control
or cardiac output control
 When pressure falls markedly below normal, nervous signals
 increase the force of heart pumping
cause contraction of the large venous reservoirs to provide more blood
to the heart
cause generalized constriction of most of the arterioles throughout the
body - more blood accumulates in the large arteries to increase the
arterial pressure
When pressure falls markedly for prolonged periods, Kidneys
Secrete pressure controlling hormones
Blood volume regulating factors

68. Long term Blood flow regulation
 Acute blood flow regulation acts within seconds to minutes, once
local tissue conditions change
 Caveat: Can adjust blood only to 75% of exact requirements
E.g., When AP increases from 100 to 175 mm Hg
Blood flow increased very little
Acute control (within in 30sec to 3 min) brings back blood to
~ 15% above normal
 Therefore acute control is rapid BUT INCOMPLETE
 Long term control regulates the blood flow to exact previous levels
E.g., If AP remains at 150 mm Hg for several days/weeks
 Therefore long term control is delayed but NEARLY COMPLETE

69. Upon change in long-term metabolic demands, tissue requires
a constant increase in supply of oxygen and other nutrients.
Hence, arterioles & capillaries increase both in size and
number within a few weeks to match the tissue needs
Long-term regulation principally changes the amount of
vascularity of the tissues, albeit by actual physical
reconstruction of the tissue vasculature
↑metabolism − ↑vascular growth
↓metabolism − ↓vascular growth
Rapid in neonates, young animals vs. slow in Old animals
Rapid in new growth tissue vs. Old, well-established tissue
Long term Blood flow regulation

70. Oxygen in Long-Term Regulation
Increases vascularity in animal tissues at high altitudes, where
atmospheric oxygen is low
Feotal chicks hatched in low oxygen have ≈ twice tissue blood
vessel conductivity vs. normal chicks
Retrolental fibroplasia − premature babies put into oxygen
tents, leads to immediate cessation of retinal
neovascularization. When infant is taken out of the oxygen tent,
blood vessels overgrow to compensate for sudden decrease in
oxygen concentration
Deficiency of tissue oxygen or nutrients, or both, leads to
formation of angiogenic factors

71. Determination of Tissue Vascularity
Determined by the MAXIMUM LEVEL OF BLOOD FLOW NEED &
not by the AVERAGE NEED OF A TISSUE
Tissue oxygen /nutrient deficiencies provokes release of vascular
growth factors, that direct angiogenesis
Vascular growth factors (angiogenic factors) are
Vascular endothelial growth factor (VEGF)
Fibroblast growth factor (FGF)
Angiogenin
Steroid hormones inhibit angiogenesis & heavy exercise
promotes angiogenesis
Extra vascularity remains constricted and opens to primarily
allow MAXIMUM BLOOD FLOW NEED, following local stimuli
such as lack of oxygen, nutrients, nerve vasodilatory stimuli, etc.

72. Collateral Circulation
Blockage of a regular blood vessel
dilatation of many existing vascular channels in first few mins.
a case of metabolic relaxation of small muscle fibers
Partial restoration, maybe 1/4th of the needs
Progressively, more channels open until 100% tissue needs are met
Growth of collateral circulation involves increase in both number
and diameter of new vessels, which continues for months
By age 60, at least one smaller branch of coronary artery is blocked
in humans
 Not detected because of collateral circulation
Heart attacks occur if blocks develop rapidly without
development of compensatory collateral circulation

73. Determinants of Blood pressure
Systolic pressure ∞ Cardiac output (exercise, myocardial
infarction)
Systolic pressure ∞ CO ∞
1
ℎ𝑒𝑎𝑟𝑡 𝑟𝑎𝑡𝑒
Diastolic pressure ∞ Peripheral resistance (PR) (resistance
offered to blood flow in arterioles in peripheral circulation)
BP ∞ Venous return (increases ventricular filling and CO)
BP ∞ Blood volume (maintains BP by controlling VR & CO)
BP ∞ Velocity of blood flow (∞ PR ∞
1
𝑐𝑜𝑚𝑝𝑙𝑖𝑎𝑛𝑐𝑒)
)
BP ∞ Viscosity of blood (η) (increases vasodilation, reduces
resistance to flow, which at 100 mm Hg is 4X vs.50 mm Hg)
BP ∞
1
Elasticity of blood vessels
BP ∞
1
Diameter of blood vessel𝑆
∞
1
conductance

74. Physiological variations in BP
Systolic pressure is more prone to changes than diastolic pressure
Increases with Age (SP/DP - newborn - 70/95, puberty 95/40,
80 year old 180/95)
Sex (5 mm. Hg higher in young women vs. similar aged males)
Body build (obese > lean)
Diurnal Variation (low in the morning, high at noon and lower
in the evening)
Nutritional Plane: high after meals vs. low in unfed state
Activity: 15-20 mm Hg. lower during sleep vs. while awake
Emotional condition (high with anxiety vs. low when calm)
Physical state (high after moderate exercise − SP raises by 20 to
30 mm. of Hg, and after sever exercise SP can increase by 40 to
50 mm. of Hg. vs. resting state)

75. Pathological Variations in BP
Hypertension: presence of persistent high blood pressure (SP
>150 & DP> 90 mm Hg). Systolic hypertension-SP is very high
Primary Hypertension: ↑SP, no underlying cause
Benign Hypertension: 200/100 long course, symptomless
Malignant Hypertension: 250/150, fatal condition
Secondary Hypertension: High BP due to underlying cause
Cardiovascular hypertension: atherosclerosis
Endocrine hypertension: hyper-secretory adrenaline gland
Renal hypertension: Glomerulonephritis, renal artery stenosis
Neurogenic hypertension: tractus solitaries lesions,↑I/C
pressure
Pregnancy toxaemia: AI disorder and vasoconstrictor hormones

76. Hypotension
Hypotension: persistent low blood pressure (SP < 90 mm. Hg)
 Primary Hypotension: ↓SP, no underlying cause
Secondary Hypotension: High BP due to underlying cause
Myocardial infarction
Hypoactivity of pituitary gland
Hypoactivity of adrenal glands
Neurogenic hypotension
Chronic diseases
Orthostatic hypotension: sudden fall in BP due to gravity,
some conditions include myasthenia gravis, tabes dorsalis,
syringomyelia and diabetic neuropathy

77. Humoral regulation of Circulation
Humoral regulation: control by substances that are secreted
and/or absorbed into the body fluids (Hormones, ions etc.)
Secreted by remote glands or in neighboring or local tissue
 Agents increasing
Blood Pressure
 Norepinephrine
 Epinephrine
 Angiotensin II
 Vasopressin
 Endothelin
 Serotonin
 Thyroxine
 Calcium (Ca2+)
 Agents decreasing Blood pressure
 Vasoactive intestinal peptide
 Bradykinin
 Histamine
 Prostaglandin, Acetyl choline
 Natriuretic peptides: ANP, BNP,
C-type NP
 Carbon dioxide
 Ions : K+, Mg2+, Na+, H+, Acetate,
Citrate, lactate, NO

78. Humoral regulation of Circulation

79. Vasoconstrictor Agents
Norepinephrine
Powerful vasoconstrictor
Released by sympathetic stimulation (exercise/stress) in
various tissues
Sympathetic stimulation of adrenal medullae secretes both
norepinephrine and epinephrine into the blood with same
effects as above
Excites heart, contracts veins & arterioles
Increases TPR & AP
Epinephrine
Less powerful vasoconstrictor
Even mildly dilates coronary arteries during increased heart
activity

80.  Angiotensin II
 Key for normal blood pressure regulation
 Powerful vasoconstrictor(arterioles)
 Increases TPR & AP
 Conc. at 1 PPM, hikes AP by more than 50 mm Hg.
Vasopressin (ADH)
key for AP regulation in injury via. body fluid volume regulation
Secreted by neurons of hypothalamus/SON (supra optic
nucleus), & stored in posterior pituitary
Not for routine regulation of vasculature function
Important in hemorrhage, increase in ADH levels increase AP as
much as 60 mm Hg
Vasoconstrictor Agents

81. Endothelin
powerful vasoconstrictor in damaged blood vessels
Effective vasoconstrictor at nanogram quantities
present in the endothelial cells of most blood vessels
Severe blood vessel damage releases endothelin
causes vasoconstriction to prevent excessive bleeding from
arteries (5 mm) size that are damaged due to crushing injury
Calcium ions
Increased conc. leads to vasoconstriction
Vasoconstriction is by contracting smooth muscles of blood
vessels
Vasoconstrictor Agents

82. Bradykinin
Powerful vasodilator in blood & tissue fluids of some organs
Activated by tissue damage/inflammation/chemicals alpha2-
globulin converted by kallikrein to kallidin
Kallidin is then processed by tissue enzymes into Bradykinin
Short lived (few minutes), deactivated by carboxypeptidases
Causes powerful arteriolar dilation and increases capillary
permeability (mainly pore size)
Even a microgram of Bradykinin can rise blood flow by 6X
Smaller amounts when applied locally causes marked oedema
Vasodilator Agents

83.  Histamine
 Released in all damaged or inflamed or allergy affected
tissues
 Source of histamine
 mast cells – damaged tissues
 basophils – blood
 Powerful vasodilator effect on arterioles, augments
capillary porosity
 allows leakage of tremendous amounts of fluid and
plasma proteins into the interstitial spaces of the tissues
causing oedema
 Mediates local allergic reactions due to its vasodilatory
and oedema producing effects
Vasodilator Agents

84. Thyroxine
Secreted by thyroid gland
Increases blood volume & force of cardiac contraction
Increases Cardiac Output
Increased metabolism, increases metabolites in tissue that
cause vasodilation & decreases in total peripheral
resistance
Increases SP, but not DP
AP is unaltered and pulse pressure changes
Vasodilator Agents

85.  ↑Ca2+ − Vasoconstriction by augmenting smooth muscle
contraction
 ↑K+ − vasodilation by inhibiting smooth muscle contraction
 ↑Mg2+ − vasodilation by inhibiting smooth muscle contraction
 ↑H+ − vasodilation, ↓H+ − vasoconstriction
 ↑CO2 in tissues – moderate vasodilation in peripheral
circulation, but significant vasodilation in cerebral blood vessels
 ↑CO2 in blood acts on vasomotor centre and stimulates
powerful sympathetic stimulated vasoconstriction across
various tissues in the body
 Acetate, Lactate & Citrate anions − Vasodilation
 Nitric Oxide - vasodilator, secreted by endothelial cells
Ions & Chemicals in Vasomotion

86. Nervous Regulation of the
Circulation

87.  Exerts wide spread control
 Rapid & short term regulation
 Controls blood flow distribution, heart pump activity & BP
 Total peripheral vascular resistance
 Blood vessel capacitance (∆Volume/∆P)
 Cardiac output
 How ?
 VASOMOTOR CENTRE responds to peripheral sensory
impulses
 Autonomic nervous system via.
 Sympathetic nervous system (resistance vessels & veins)
 Parasympathetic nervous system (heart)
Nervous Regulation

88. Vasomotor system
Sympathetic VM nerve fibers
leave spinal cord through all
thoracic and 1 or 2 lumbar
spinal nerves, enters
sympathetic chains & exits
through specific sympathetic
nerves, innervate
Vessels of viscera & heart
Vessels of peripheral areas
 No innervation into Capillaries,
Precapillary sphincters, &
metarterioles
 Innervation of small arteries &
arterioles allows sympathetic
regulation of resistance

89. Vasomotor
system

90.  Located in upper medulla & pons region
 Three components
 Vasomotor centre
 Vasoconstrictor area
 Vasodilator area
 Sensory area
 Vasoconstrictor fibers
 Vasodilator fibers
 Parasympathetic vasodilator fibers
 Sympathetic vasodilator fibers
 Antidromic vasodilator fibers
Vasomotor system

91.  Vasoconstrictor area:
 pressor /cardio-accelerator area, lateral side
 sends impulses to vasculature & cardio-accelerator area
via. sympathetic vasoconstrictor fibers
 under hypothalamus & cortex control
 Result: Vasoconstriction, ↑HR, ↑AP
 Vasodilator area:
 depressor area/cardio-inhibitory area, medial side
 inhibits vasoconstrictor area & cardioinhibitor
 Under cortex, hypothalamus, Chemo- & Baro-, receptors
 Result: Vasodilation, ↓HR, ↓AP
 Sensory area:
 NTS, posterolateral part of medulla & pons
 Peripheral sensory impulses via. GP, Vagal nerves &
baroreceptors
 Result: Controls Vasoconstrictor & Vasodilator area
Vasomotor centre

92. Vasoconstrictor fibers
 Fiber endings secrete noradrenaline
 Acts on α-adrenergic receptors of smooth muscle
 Predominant role in BP regulation than Vasodilator
fibers
 maintenance of vasomotor tone (vasoconstrictor
tone) in blood vessels (continuous impulse discharge)
 Result: Vasoconstriction & ↑ in BP
Vasodilator fibers: three types
 Parasympathetic vasodilator fibers
dilatation of blood vessels by releasing
acetylcholine
Result: ↓ in HR & a small ↓ in contractility

93. Sympathetic vasodilator fibers
vasodilatation by secreting acetylcholine from
sympathetic cholinergic fibers (e.g., exercise)
origin: cerebral cortex - relayed to spinal cord via.
hypothalamus, midbrain & medulla
Mainly important in skeletal muscle during exercise
Result: Vasodilation & ↓ in BP
 Antidromic vasodilator fibers
impulses produced by cutaneous receptor (e.g., pain
receptor) & pass through sensory nerve fibers
part of these impulses pass in opposite direction & reach
blood vessels & dilates blood vessels
Antidromic/axon reflex, fibers are antidromic vasodilator
Result: Vasodilation & ↓in BP
Vasodilator fibers

94.  Vasomotor centre regulated by higher centres of brain
 Cerebral cortex
 Area 13 of brain, read emotions
 Sends signals to vasomotor center
 Vasomotor tone increase &↑BP
 Hypothalamus
 Posterior & lateral hypothalamic nuclei activation
 Signals to vasomotor center causing vasoconstriction
 Signals to PON causes vasodilation & ↓BP
 Respiratory Centre – Respiratory pressure waves
 onset of expiration, ↑BP by 4 - 6 mm of Hg
 BP↓ during inspiration & expiration - spillover signals
from respiratory centre to vasomotor centre
 Thoracic cavity pressure changes venous return & CO
Higher brain centres

95. Carotid baroreceptors
Located in Carotid sinus
Afferents form Hering nerve, a branch
in glossopharyngeal (IX, C) to NTS
Relays BP changes in 50 − 200 mm. Hg
Aortic baroreceptors
Located in aortic arch adventitia
Afferents form aortic nerve, a distinct
branch of vagus (X, C) to NTS
Relays BP changes in 100 − 200 mm. Hg
Baroreceptors/Pressoreceptors
 Respond to changes in BP & relays to vasomotor center
 Major role in short term regulation of blood pressure
 Baroreceptors helps to rapidly adjust for pressure changes due
to altered posture, BV, CO & TPR

96. Baroreceptors
Baroreceptor stimulation (rapid increase in BP due to
sympathetic α – adrenergic stimulation) reduces heart rate
RR interval ∞
𝟏
𝑯𝒆𝒂𝒓𝒕 𝒓𝒂𝒕𝒆
Heart rate as a function of
increasing arterial pressure
during α - adrenergic
stimulation
Within 120 - 150 mm Hg, a
linear relation exists between
HR decrease & arterial
pressure increase
Long term increase in BP due to Baroreceptor loss is called
Neurogenic hypertension

97. Baroreceptors
Receptor firing increases with increased arterial pressure
More number of impulses carried away from afferents to brain

98.  Respond to changes in PO2, PCO2 & H+ ions
 Located in carotid body and aortic body
 Chemoreceptors exert their effects on respiration
 Consists of two cell types
 Type I/ glomus cells
 glomus cells have afferent nerve endings
 Type II/ sustentacular cells
 glial cells, supporting glomus cells
 Nerve innervations: carotid body - Hering nerve, aortic body -
aortic nerve
 Function
 Activated by hypoxia, hypercapnea & higher H+ ions
 Send inhibitory impulses to vasodilator area
 Hyperpnea, ↑ catecholamine secretion, tachycardia
 Vagal tone decreases and heart rate ↑
Chemoreceptors

99.  Mechanism of action of baroreceptors & chemoreceptors
together constitute sinoaortic mechanism
 Vasomotor centre regulates vasoconstriction/vasodilation
 Baroreceptors & Chemoreceptors sends sensory inputs to
vasomotor centre for short term regulation of BP
 Sensory nerve fibers from baroreceptors reach NTS,
located adjacent to vasomotor centre in medulla
oblongata
 Supplying nerves are called buffer nerves
 Mechanism is also called pressure buffer mechanism
 Regulates heart rate, blood pressure & respiration
BP Regulation – Sinoaortic Mechanism

100.  Increased blood pressure stimulates Baroreceptors
 Mainly by rising BP than steady BP
 Response depends on rate of increase in BP
 Result: decreased PR & CO, brings BP back to normal
Pressure Buffer Mech.− Baroreceptors
stimulatory impulses

101. Decreased blood pressure
Decreased blood flow to chemoreceptors
Decreased O2, increased CO2 & H+ ion
Activate Chemoreceptors
Stimulate Vasoconstrictor centre
Blood pressure & blood flow increases
Chemoreceptors

102. Atrial & Pulmonary Artery Reflexes
 Low pressure stretch receptors in atria, ventricles & pulmonary
arteries
 Cardiopulmonary receptors – volume receptors
 Minimize AP variations caused by volume changes
 Detect AP changes in low pressure areas caused by blood volume
changes (pulmonary artery, atria etc.)
 Example: If 300 mL blood infused to an adult dog
 AP rises ≈ 15 mm Hg, when all Receptors intact
 AP rises ≈ 40 mm Hg, when all receptors intact except
Baroreceptors
 AP rises about ≈ 100 mm Hg, when all receptors intact
except Baroreceptors & low pressure receptors

103. Increased atrial
pressure
Increases Heart Rate
Stretching of SA
node
Increased pulse
frequency
Vasomotor Centre
Atrial stretch
receptors
Vagus
Sympathetic
 Prevent damning of
blood in veins,
atria & Pulmonary
circulation
Bainbridge Reflex

104. Kidneys — Volume Reflex
 Atrial Kidneys — Volume Reflex mechanism of BP control
↓Blood volume, ↓AP
Stretch of atria
Reflex dilation of afferent arterioles of glomerulus
& signals from atria to hypothalamus
↑Efferent arteriolar resistance
↑Glomerular capillary pressure (↑GFR )
↑Fluid filtration volume
↓Decreased reabsorption (↓ADH secretion)
↑Blood volume, ↑AP

105. ↓Blood flow to the vasomotor centre in the lower brain stem
↑Nutritional deficiency/ Cerebral ischemia
↑Firing of vasoconstrictor, Cardio-accelerator neurons
↑Systemic arterial pressure rises as high as heart can pump
↑CO2, lactic acid concentration in brain VM centre
↑Sympathetic vasomotor nervous centre activity
CNS Ischemic Response
 Very powerful & generalized vasoconstrictor response
 Emergency & rapid pressure control system, last ditch stand
 Only kicks in at low pressure range (< 60 mm of Hg)

106. Abdominal Compression Reflex
Stimulation of
vasoconstrictor
system
Baroreceptor reflex
Chemoreceptor reflex
Other factors
Vasomotor Centre
↑Abdominal muscle tone
Compression of abd.
musc. & Venous reservoirs
Translocation of blood
towards the Heart
Increases CO
Increases AP

107. Skeletal muscle
contraction during
Exercise
Vasomotor Centre
↑Abdominal muscle tone
& compression of venous
reservoirs
Compression of blood
vessels throughout the
body
Translocation of blood
towards Heart & Lungs
Increases CO
Increases AP
Spinal nerves
Exercise induced increases in CO & AP

108.  Cause rapid and significant increase in BP
 Entire repertoire of vasoconstrictor and cardio-accelerator
function of sympathetic nervous system is stimulated
 To counterbalance when not needed, the parasympathetic
fibers in vagus nerve, sends inhibitory signals to heart
 All resistance vessels are vasoconstricted, ↑TPR, ↑BP
 Venoconstricton moves blood to heart ↑CO & ↑BP
 Sympathetics directly stimulate heart to increase both
its rate and strength of cardiac muscle contractility (2-3X
normal volume of blood can be pumped)
 Vasodilatory control of circulation is not of significance
in normal state, but in exercising subject , vasodilation
may allow for anticipatory increase in blood flow
Neural regulation of BP - Summary

109.  Vasovagal syncope
 Intense emotional disturbances causes activation of
vasodilatory fibers and inhibits heart via cardio-
inhibitory vagal signals
 Rapid decrease in Blood pressure & flow to brain
causes unconsciousness
 Disturbing thoughts in cerebral cortex may be involved
 Pathway includes hypothalamus, vagal nerve fibers and
spinal cord vasodilator fibers
 Also known as “emotional fainting”
Examples of Nervous Regulation of BP

110.  Exercise
 Greater demand for nutrients & oxygen in muscle tissue
 Sympathetic stimulation ↑BP & blood flow
 Demands are met by local vasodilation & ↑blood flow
 BP↑ by 30-40 % & blood flow by 2 X normal
 supported by activating vasoconstrictor & cardio-
acceleratory areas of the vasomotor centre
Extreme fright
Extra blood flow to supply nutrients to manage the
dangerous situation
BP raises by 2 X normal within few seconds, an alarm
reaction
Examples of Nervous Regulation of BP

111. Long term Regulation of Arterial
Pressure by Kidneys

112. An evolutionary conserved mechanism in all vertebrates
Primarily carried out by modulating
ECF volume in response to arterial pressure (AP) changes
Renin-Angiotensin-Aldosterone mechanism
Physiological variables of importance includes:
Circulatory variables
ECF volume
Blood volume
Cardiac output
Total Peripheral resistance
Renal variables
Perfusion pressure in glomerulus
Urinary intake/output of salt & water (Kidneys)
Long term Regulation of Arterial Pressure

113. Renal Function Curve
When Arterial Pressure increase, Kidney acts to cause
Pressure Diuresis: increased urinary output
Pressure Natriuresis: increased salt output
AP (mm Hg)
Urine output
(folds)
< 55 0
≈ 90 normal
≈150 4 X normal
≈190 8 X normal
Renal regulation of AP is an ‘Infinite Feedback Gain’ mechanism

114. How Pressure Diuresis Control AP?
 Renal–Body Fluid System for arterial
Pressure Control
 In an experimental dog, first all
nervous reflex mechanisms of AP are
blocked
 400 mL blood was intravenously
infused, after 1 hour
 CO − ↑ 2 folds
 AP − ↑ 2 folds
 Pressure diuresis: UO − ↑12 folds
 CO & AP returned normal in 1 hour
 a case of volume loading hypertension, corrected by kidneys

115. Two factors determine arterial pressure level
renal output of water & salt (renal output curve)
level of net water and salt intake (salt water intake
curve/line)
 If, renal output of salt & water
= intake of salt and water, the
pressure will always adjust
back to equilibrium point
(MAP = 100 mm Hg.)
AP control by Renal–Body Fluid System

116. How do the equilibrium point change?
1. Changing the pressure level of the
renal output curve for salt & water
E.g: Kidney disorder, ↑AP,
equilibrates at 150 mm Hg
 Two ways
2. Changing the level of the water &
salt intake
E.g: higher intake level (4 fold)
equilibrates ) AP at 160 mm Hg

117. Hypervolemia & AP
 In an experimental dog
 Kidney volume ↓ to 30% normal
 Salt intake ↑to 6 X normal
 Acute effects (2 days)
 Arterial pressure (AP) − ↑30%
 ECF volume (ECFV) − ↑33%
 Blood volume (BV) − ↑20%
 Cardiac output (CO) − ↑40%
 Total resistance (TPR) − ↓13%
 Long-term effects (2 Wks)
 ECFV, BV, CO restored
 Secondary rise in TPR – ↑33%
 Arterial pressure – ↑40%

118. Volume loading & Arterial Pressure Changes
↑ECF in intercellular spaces & ↑Blood volume (BV)
↑Venous return (VR)
↑Arterial Pressure (AP)
↑Right ventricular filling pressure
↑Cardiac Output (CO) Autoregulation
↑Total Peripheral resistance (TPR)
Excess salt & water intake/Fluid transfusion
↑Mean Circulatory filling pressure

119. Renal Regulation of Arterial Pressure
Kidneys removes excess water & salt (↑Urinary Output)
Systemic arterial pressure is brought back to normal
Regulation
by kidneys
↑ ECF in intercellular spaces & ↑Blood volume
↑Venous return
↑Right ventricular filling pressure
↑Cardiac output, CO Autoregulation
↑Total Peripheral resistance (TPR)
↑Arterial Pressure

120.  Kidney mass/function is essential for AP regulation
 70% Kidney mass removed in Dogs:
 Arterial Pressure increases with increased Na+ & H20 intake

121. 𝐀𝐫𝐭𝐞𝐫𝐢𝐚𝐥 𝐏𝐫𝐞𝐬𝐬𝐮𝐫𝐞 = 𝐂𝐎 𝐗 𝐓𝐏𝐑 (𝐓𝐨𝐭𝐚𝐥 𝐏𝐞𝐫𝐢𝐩𝐡𝐞𝐫𝐚𝐥 𝐫𝐞𝐬𝐢𝐬𝐭𝐚𝐧𝐜𝐞)
Arterial pressure can be altered
either by changing CO or TPR or
both
In conditions where CO > normal,
AP maintained by reducing TPR
E.g., Hyperthyroidism
In conditions where CO < normal,
AP maintained by increasing TPR
E.g., Hypothyroidism
When both CO & TPR are normal
(100%), AP is also normal

122. Renal regulation of Arterial Pressure
A few mm. Hg rise in AP can increase water (Pressure Diuresis)
& salt (Pressure Natriuresis), excretion
Excretion of water & salt by kidney is sensitive to AP changes
Long-term AP control is related to body fluid homeostasis
Works primarily by regulating ECF volume via.
Thirst center: High osmolality of ECF stimulates the thirst centre
in the brain causing to drink extra amounts of water to return
the extracellular salt concentration to normal, increase in ECF
volume, increase in BP
ADH hormone (Pressure diuresis): increased salt in extracellular
fluid rises tissue osmolality , which then releases ADH from
posterior-Pituitary. ADH causes water retention, thereby
increasing water level in ECF & restores ECF osmolarity, volume
and BP

123. Renin - Angiotensin mechanism
Renin secretion is stimulated by
↓arterial blood pressure, ↓ECF volume, ↑ SNS activity, ↓
load of sodium and chloride in macula densa.
Angiotensin II, III, IV
1st set of actions: direct renal effects (very potent):
constriction of renal arterioles, ↓blood flow, ↓ glomerular
filtration, ↑salt & water retention, ↑ECF volume & ↑AP
2nd set of actions: action via. Aldosterone: stimulates
aldosterone secretion, reabsorption of sodium from renal
tubules,↑water reabsorption, ↑ECF volume, ↑blood
volume & ↑AP
Renin-Angiotensin mechanism amount of salt that accumulates in
the body is the main determinant of the extracellular fluid volume.
RA mechanism is key in mode of BP control

124. Increasing renal retention of salt &
water by angiotensin infusion
E.g., Blockage of Renin-angiotensin
pathway, MAP equilibrates to 75
mm. of Hg. & infusion of
angiotensin (2.5 x normal) ↑MAP
equilibration to a higher level at
115 mm. Hg
Effects of Angiotensin on BP

125. Renin- Angiotensin mechanism

126. After haemorrhage:
Acute decrease of the
arterial pressure to 50 mm
Hg
Arterial Pressure rose back
to 83 mm Hg when the
renin-angiotensin system
back to function
Renin- Angiotensin mechanism

127.  Rapid/Quick
 Exclusively nervous reflexes
 CNS ischemic response
 Baroreceptor reflex
 Chemoreceptor reflex
 Intermediate
 Renin-Angiotensin System
 Stress relaxation of vasculature
 Shift of fluids in and out of circulation to adjust
blood volume
 Long-term
 Renal body fluid system
Summary of arterial pressure regulation

128. Arterial Pressure Regulation Summary
1. Within seconds
 Baroreceptor mechanism
CNS ischemic response
Chemoreceptor mechanism
2. Within several minutes
 Renin-Angiotensin
vasoconstrictor mechanism
 Stress relaxation of vasculature
 Shift of fluids through capillary
walls in tissues
3. Within hours, days & cont.
 Renal body fluid control
 Aldosterone control
 CNS ischemic response

129. Renin- Angiotensin mechanism
Decreased BP
BP restored to normalcy

130. ↑Salt & water Reabsorption
Decreased Arterial Pressure
↑Renin secretion by Kidney (JG apparatus)
Systemic Arterial Pressure is restored to normalcy
Angiotensin II, III, IV
Activates Angiotensinogen (renin substrate)
Angiotensin I
Vasoconstriction
Angiotensin converting enzyme (lungs)
Adrenal cortex
Aldosterone
Kidneys
↑ECF and blood volume
Cardiovascular system
Renin- Angiotensin mechanism

131. Renin-angiotensin system
an automatic feedback mechanism
Keeps BP in normal range even when salt intake
changes

132. Veins

133. Coronary Circulation
 Two coronary arteries
 Right artery supplies whole of the RV & posterior wall of LV
 Left artery supplies anterior & lateral wall of LV
 Right & Left arteries divide into epicardiac arteries that
branch into final arteries or intramural vessels

134. Coronary Circulation
Blood volume in CC is ≈200 mL/minute.
4-5% of cardiac output
65 - 70 mL/minute/100 g of cardiac
muscle
Blood flow
Autoregulation
Phasic, ↓in systole & ↑in diastole
Flow↓: Myocardial pressure > Aortic pressure
Changes when AP is out of 60 - 150 mm Hg range
 Physiological shunt:
 Deoxygenated blood in Thebesian veins → cardiac chambers
 deoxygenated blood from bronchial circulation → pulmonary vein

135.  Factors affecting flow
 Oxygen: Higher myocardial
O2 extraction, hypoxia
 Metabolic factors:
Adenosine, K+, H+, CO2, NO,
kinin, prostacycline
 Coronary perfusion pressure
in LV
= ADP – LVEDP
 Nervous factors (ANS):
 Sympathetic NS
 Parasympathetic NS
Coronary Circulation

136. Coronary Circulation - Venous Drainage
 Coronary sinus from aorta, anterior coronary veins from RV
 Thebesian Veins from myocardium
 Arterio-sinusoidal & -luminal vessels from arterioles

137. Foetal Circulation
Foetal lungs are nonfunctional
Placenta = Foetal lung
Site of gas & nutrient exchange is placenta
Heart development completes at 4th week of gestation
Foetal HR is ≈65 BPM, ↑ to ≈140 BPM before birth
Foetal heart pumps large quantity of blood into placenta
Umbilical veins collect blood from placenta & passes
through liver & then enters RA via. IVC
Umbilical vein blood enters IVC via. Ductus Venosus
Blood flows from RA into LA via. Foramen Ovale

138. Anatomy of Foetal Circulation

139. Fetal Circulation Vs. Adult Circulation
UV UA
 55% Foetal CO passes through Placenta
 Umbilical venous blood has 80% O2 Sat. vs. 98% in adult arteries
 Ductus Venosus diverts UV blood to IVC, O2 sat. 67%
 Portal & systemic venous blood is 26% O2 sat.
 Blood from IVC → LA via patent Foramen Ovale
 Blood from SVC → RV → Pulmonary artery
 Pulmonary artery → Aorta via. Ductus Arteriosus
 Unsaturated blood in RV perfuse trunk & lower body of the fetus
 Better-oxygenated blood from LV perfuses head
 From aorta, blood → umbilical arteries → placenta
 Blood in aorta & umbilical arteries is ≈ 60% O2 Sat.

140. Pulmonary circulation in Foetus
Foetal & new-born tissues are resistant to
hypoxia
O2 saturation of maternal blood in the
placenta is very low vs. Foetal blood
O2 affinity, of Hgb F > Hgb A, binding of Hgb
F with 2,3-DPG is less vs. Hgb A
DA & FO makes left & right hearts parallel
pumps
Placental circulation ceases at birth & TPR
increases suddenly
Aasphyxiation at birth opens up foetal lungs
Higher –ve Intrapleural pressure (–30 to –50
mm Hg) causes foetal lung expansion

141. Pathophysiological aspects
 Blood flow to LV is mainly during diastole, especially blood flow in
subendocardial portions of heart
 LV systolic pressure > Aortic pressure (∆P = −1) – Minimal flow
 Subendocardial area of heart are more prone to ischemia as no
blood flow during systole
 Exercise: Coronary blood flow ↑ if myocardium metabolism ↑
 ↓Aortic diastolic pressure – ↓coronary blood flow
 Tachycardia: When HR ↑, Diastole period ↓ − ↓ LV coronary
blood flow
 Stenosis of Aortic valves: Requires high LV pressure than Aorta to
eject blood, more stronger systole – less LV perfusion
 Congestive heart failure: ↑ Venous pressure – ↓ EPP – ↓coronary
flow

142. Cardiac Output & Venous Return Curves

143. Cardiac Output (CO): the quantity of blood pumped into aorta
each minute by heart or the quantity of blood that flows through
the circulation at any point of time
Venous Return (VR): the quantity of blood flowing from veins into
right atrium each minute
Ideally, CO = VR, in young men, CO = 5.6 L/min, women = ~4.9 L/min
Factors the affect CO:
 Basal metabolic rate
 Physical activity, e.g., exercise
 Chronological age
 Body size
Cardiac index: CO per square meter of body surface area
E.g., Bd. Wt. = 70 Kgs, SA = 1.7 m2 , 3L/min/ m2
Cardiac Output & Venous Return

144. Cardiac Output & Venous Return
 Cardiac Output is controlled by Venous Return
 VR matches the sum of the local blood flow regulation in all
local tissues of the body
 CO regulation is the sum of all local blood flow regulations
 In unstressed condition, heart is not a major control node of
CO, but rather VR, Frank Starling law of heart
 When TPR ↑, CO ↓
 Cardiac Output =
𝑨𝒓𝒕𝒆𝒓𝒊𝒂𝒍 𝑷𝒓𝒆𝒔𝒔𝒖𝒓𝒆
𝑻𝒐𝒕𝒂𝒍 𝒑𝒆𝒓𝒊𝒑𝒉𝒆𝒓𝒂𝒍 𝒓𝒆𝒔𝒊𝒔𝒕𝒂𝒏𝒄𝒆
 Peripheral factors that affect CO: CO decreases
 ↓ blood volume
 Acute venodilation
 Obstruction of large veins
 ↓tissue mass, e.g, skeletal muscle atrophy

145.  Factors increasing CO (Hyper-effective hearts) – Left shift
 Nervous system regulation: SNS stimulation & PSN inhibition,
increases HR (2-3X) & Cardiac contractility (2X)
 Hypertrophy of heart
 Chronically high workload ↑myocardial mass & contractility
 Excitation of Cardiac nerves
 Factors decreasing CO (Hypo-
effective hearts) – Right shift
 Decreased functioning of heart
 Coronary blockage, Nervous
inhibition, Arrhythmias, Valvular
heart diseases, Hypertension,
myocarditis, hypoxia, congenital
heart disease
 Shift of plateau to right
CO↑
↓CO

146.  Intact Nervous signal:
Dinitrophenol - metabolic
booster & Vasodilator
Enhanced cardiac output
almost 4X, and no significant
changes in AP
Compromised Nervous signal:
 Dinitrophenol injection led
to little increase in CO, & a
significant drop in AP
 Physical exercise is another example where CO increase due to
enhanced metabolism & VR, nervous signals keeps AP unchanged

147. CO↑, when
TPR ↓
↑ Diameter
 ↑VR
CO↓, when
↓ Heart Pumping
↓Venous return
 MI
Myocarditis
Valvular diseases
Metabolic disorders

148. Extracardiac pressure
 Pressure outside the heart, intra-pleural pressure (IPP)
 Ranges –6 to –2 mm Hg (Avg. – 4 mm Hg)
 High intra-pleural pressure − venous return & CO – ↓
 E.g., open heart surgeries & in positive pressure ventilation
 Low intra-pleural pressure − venous return & CO – ↑
 E.g., negative pressure breathing
 Rise in IPP shifts CO curve to right by same amount of pressure
increase in right atrium
 Factors changing IPP
 Respiration (±2 to ±50 mm Hg)
 Negative pressure ventilation
 Positive pressure ventilation
 Opening thoracic cage
 Cardiac Tamponade Rt)

149. Venous Return
Three factors regulate Venous return (VR)
Right atrial pressure: backward force on the veins to impede
blood flow from veins into RA
Mean systemic filling Pressure: represents degree of filling of
the systemic circulation that forces the systemic blood towards
RA
Resistance to blood flow: impedance to flow of blood between
the peripheral blood vessels and RA
When RA pressure increases, VR decreases due to back-pressure in
RA, & CO eventually decreases
Venous return curves demonstrate relationship between venous
return & right atrial pressure
When all nervous reflexes blocked, VR will be zero when RA
pressure ≥ +7, a pressure called ‘mean systemic filling Pressure’

150. Venous return curves: curves demonstrating relationship
between venous return & right atrial pressure
When right atrial pressure falls
< 0, increase in VR almost ceases
≤ –2 mm Hg, VR will reach a plateau
– 20 to – 50 mm Hg, plateau is maintained
Reason: plateau is due to collapse of veins entering the chest
If AP = VP, all flow in the systemic circulation ceases at a pressure of
7 mm Hg, termed Mean Systemic Filling Pressure (+7)

151.  Mean systemic filling pressure (Psf)
increase with increase in blood volume
 ↑ in mean Circulatory filling pressure
is steeply linear with increase of even
small quantities of blood
 Nervous system activity
 Sympathetic stimulation can cause
vasoconstriction, decrease in total
capacity of circulatory system, and
increase (Psf) by 2.5 times of
normal (from 7 to 17 mm Hg)
 With PSN activity, (Psf) change can
decrease vs. normal (from 7 to 4
mm Hg)
 the greater the difference between the mean systemic filling
pressure and the right atrial pressure, the greater is the VR

152.  Resistance to venous return, VR =
Psf − PRA
𝑹𝑽𝑹
 Psf = Mean systemic filling pressure
 PRA = Right atrial pressure
 RVR = resistance to venous return
5 =
7 −𝟎
𝑹𝑽𝑹
= RVR = 7/5 = 1.40 mm Hg./L
 When resistance to flow is 1/2x
normal, flow 2X normal
 When resistance to flow is 2X
normal, flow is ½X normal

153. Cardiac functional Curves (CO & VR)
 Conditions in normally functioning Heart &
Vasculature
CO = VR; RAP = Psf
Momentary hearts pumping ability = CO
Momentary state of flow from systemic
circulation to heart = VR
A 20% increase in blood volume
↑Psf (16 mm Hg), ↑ CO & VR to 3X
shifted upwards & right
↑blood volume→ Venoconstricton,
↓resistance to VR
Finally, CO & VR ↑2.5 - 3X normal and RAF to +8 mm Hg
 Compensatory response to increased CO: ↑capillary pressure, venous
dilatation by stress relaxation, ↑TPR, ↑resistance to venous flow,
↓Psf to normal

154.  Sympathetic inhibition by spinal
anaesthesia or using hexamethonium:
 Psf falls to 4 mm Hg
 Effectiveness of heart pump ↓ to
80% of the normal
 CO falls to about 60% of the normal
 Sympathetic stimulation:
 Heart becomes a stronger pump
 Increases Psf – 16 mm Hg
 Increases resistance to VR
 Opening of an Arteriovenous fistula:
 Point A: normal
 Point B: immediate to o/p AV fistula
 Point C: After sympathetic stimulation
 Point D: After several weeks after o/p

155. Circulatory Shock: generalized inadequate blood flow through
the body that causes damage to body tissues (mainly
inadequate supply of oxygen and other nutrients to the body
cells)
What is a common culprit in terms of hemodynamics?
Decreased cardiac output!!!
What decreases CO?
Factors that ↓Cardiac pumping activity
(Cardiogenic Shock)
e.g., myocardial infarction, cardio-toxicity,
valvular dysfunction, arrhythmias
Factors that ↓Venous Return
e.g., ↓blood volume, ↓decreased vascular
tone, obstruction to blood flow
Circulatory Shock

156. Circulatory Shock without decreased cardiac output:
Excessive metabolism, so normal CO is not insufficient
Tissue perfusion abnormalities causing a major portion of CO
going into vessels other than those that perfuse tissues
Commonality in most cases of shock:
inadequate nutrients delivery to critical tissues organs
inadequate removal of cellular waste products from the tissues
Circulatory Shock

157. Tissue deterioration is the end in
circulatory Shock. Regardless of
cause, in advanced stages, shock
itself breeds more shock, and spirals
down into a vicious cycle
Circulatory Shock Detection
 Arterial pressure is used to assess circulatory sufficiency & cardiac
output in shock. Limitation: Sometimes, AP can be misleading. In case
of haemorrhages involving severe blood loss, AP falls simultaneous to
diminished CO
Insufficient blood flow causes the tissues to continuously
deteriorate, which leads to progressive decline in CO and tissue
perfusion until death